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Nanotechnology and Skin Delivery: Infinitely Small or Infinite Possibilities?
By: Johann W. Wiechers, PhD, JW Solutions
Posted: December 19, 2008, from the January 2009 issue of Cosmetics & Toiletries.
- Figure 1. Theoretical predictions of particle penetration
- Figure 2. Histological sections demonstrating the penetration depth
- Figure 3. Kinetics of the storage of nanoparticles
- Figure 4.The effect of particle size on the UV attenuating properties of titanium dioxide.
- Figure 5. Schematic representation of the size-dependent occlusive effect of lipid nanoparticles
- Figure 6: Cumulative amount of ketorolac
page 3 of 13
Having established that there are indeed nanoparticles in the immediate environment, does this particulate matter penetrate human skin under normal application conditions? Let us zoom in on the principle of skin penetration of nanoparticles.
For ideal skin penetration, the penetrating molecule should have an octanol/water partition coefficient, K, of 10-100 (or 10log K = 1-2); its molecular weight should be below 500 Dalton; the molecule should be nonionized in the pH range (4.7-7.4) it will encounter during its transport through the skin; the molecule should have a high dipole moment and it should be a liquid at physiological temperatures.9 Particles, on the other hand, consist of many molecules and will therefore have a molecular weight that is much greater than 500 Dalton. They are also, by definition, not solubilized. Particles therefore do not have the optimal characteristics to penetrate human skin.
Professor Mike Roberts of the University of Queensland, Australia, calculated the exposure levels of nano-sized materials on purely theoretical grounds (see Figure 1).10 He argued the following:
1. Basic pharmacokinetics dictates that the steady-state epidermal exposure concentration of a compound is equal to the maximum flux of this compound divided by the sum of the desquamation clearance, the epidermal clearance and the return penetration (see Reference 2 for details).
2. The maximum flux of a compound can be predicted (for solubilized molecules) from the molecular weight of the compound.11 Roberts modified this relationship to predict the same from the molar volume.